Spinal Muscular Atrophy: Differential Diagnosis – Childhood Onset (> 6 months and older)

Spinal Muscular Atrophy: Differential Diagnosis – Childhood Onset (> 6 months and older)

Spinal Muscular Atrophy (SMA) that presents after 6 months of age will include the second most common presentation of SMA, type 2 SMA, and the least commonly observed form of childhood onset SMA, type 3.1 The typical presenting symptoms of types 2 and 3 SMA, progressive symmetric proximal more than distal weakness and reduced tone following a period of normal development,2 invites a list of differential diagnoses worth of consideration, and delay in the diagnosis of SMA types 2 and 3 suggests that evaluation for SMA mimics impede efficient diagnosis.3 The differential diagnosis of types 2 and 3 SMA are broken down by categories as follows:


Guillain-Barré syndrome is the most common cause of acute flaccid paralysis in previously healthy children.4 Typically, the weakness in Guillain-Barré syndrome ascends acutely from distal sites differentiating it from the more insidious onset and proximal location associated with SMA.5 Acute transverse myelitis can produce weakness with loss of reflexes in children and may represent the first clinical evidence of a chronic demyelinating autoimmune disease.6


Many of the congenital neurodegenerative disorders discussed in the SMA: Differential Diagnosis—Prenatal/Neonatal topic could present as a later onset variant and should be considered in the differential for infants and young children with new onset of weakness.7 One notable example would be the juvenile form of hexosaminidase A deficiency (Tay-Sachs disease) which can begin at age 2, present with weakness and poor coordination, but lack the diagnostic findings in the classic infantile onset form such as a cherry red spot.8 The mitochondrial myopathies may also begin at virtually any age in childhood but typically have other symptoms such as ptosis or sensory loss that differentiate them from SMA.9 Congenital neuropathies, with Charcot-Marie-Tooth disease being the prototype, present can become symptomatic in this group but unlike SMA will have a significant sensory component evident on electrodiagnostic testing.7

The muscular dystrophies present with progressive weakness after normal development in an age range (age 2-3) overlapping SMA types 2 and 3; thus, the diagnoses of Becker and Duchenne muscular dystrophies should be considered.7 Cognitive dysfunction is a co-morbidity with muscular dystrophies that would not be expected to be present in SMA. Patients with SMA 3 may present with symptoms similar to limb girdle muscular dystrophies, but the presence of fasciculations and neurogenic (versus myopathic) electromyelograph findings suggests SMA as the diagnosis.10


With the advent of poliovirus vaccination, poliomyelitis due to acute poliovirus infection is no longer a common cause of flaccid paralysis but other enteroviruses and West Nile virus can cause an often asymmetric paralysis in the lower extremities.5


Nutritional deficiencies in copper and vitamin B12 can cause progressive myelopathy with gait instability with a strong anatomical localization to the posterior columns of the spinal cord that suggests a cause other than SMA.11


Spinal cord masses, intervertebral disk herniation, vertebral fracture with displacement, and spinal cord infarct are in the differential diagnosis for any acute weakness especially with a recent history of trauma to the dorsum or spine.6


1. Belter L, Cook SF, Crawford TO, et al. An overview of the Cure SMA membership database: Highlights of key demographic and clinical characteristics of SMA members. J Neuromuscul Dis. 2018;5(2):167-176.

2. Chabanon A, Seferian AM, Daron A, et al. Prospective and longitudinal natural history study of patients with Type 2 and 3 spinal muscular atrophy: Baseline data NatHis-SMA study. PLoS One. 2018;13(7):e0201004.

3. Lin CW, Kalb SJ, Yeh WS. Delay in Diagnosis of Spinal Muscular Atrophy: A Systematic Literature Review. Pediatr Neurol. 2015;53(4):293-300.

4. Karalok ZS, Taskin BD, Yanginlar ZB, et al. Guillain-Barre syndrome in children: subtypes and outcome. Child’s nervous system : ChNS : official journal of the International Society for Pediatric Neurosurgery. 2018.

5. Garg N, Park SB, Vucic S, et al. Differentiating lower motor neuron syndromes. J Neurol Neurosurg Psychiatry. 2017;88(6):474-483.

6. Tavasoli A, Tabrizi A. Acute Transverse Myelitis in Children, Literature Review. Iran J Child Neurol. 2018;12(2):7-16.

7. Menezes MP, North KN. Inherited neuromuscular disorders: pathway to diagnosis. J Paediatr Child Health. 2012;48(6):458-465.

8. Kaback MM, Desnick RJ. Hexosaminidase A Deficiency. In: Adam MP, Ardinger HH, Pagon RA, et al., eds. GeneReviews((R)). Seattle (WA): University of Washington, SeattleUniversity of Washington, Seattle. GeneReviews is a registered trademark of the University of Washington, Seattle. All rights reserved.; 1993.

9. Broomfield A, Sweeney MG, Woodward CE, et al. Padiatric single mitochondrial DNA deletion disorders: an overlapping spectrum of disease. Journal of inherited metabolic disease. 2015;38(3):445-457.

10. Alsaman AS, Alshaikh NM. Type III spinal muscular atrophy mimicking muscular dystrophies. Pediatr Neurol. 2013;48(5):363-366.

11. Plantone D, Primiano G, Renna R, et al. Copper deficiency myelopathy: A report of two cases. The journal of spinal cord medicine. 2015;38(4):559-562.